Deuterated Linoleic Acid Attenuates the RBC Storage Lesion in a Mouse Model of Poor RBC Storage

Kim, Christopher Y.; Johnson, Hannah; Peltier, Sébastien; Spitalnik, Steven L.; Hod, Eldad A.; Francis, Richard O.; Hudson, Krystalyn E.; Stone, Elizabeth F.; Gordy, Dominique E; Fu, Xiaoyun; Zimring, James C.; Amireault, Pascal; Buehler, Paul W.; Wilson, Robert B.; D’Alessandro, Angelo; Shchepinov, Mikhail S.; Thomas, Tiffany

doi:10.3389/fphys.2022.868578

Cited by 14 publications

(13 citation statements)

References 66 publications

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“…The similarity between the Hb increment observed in a mouse model and in the human study supports the concept that a mouse model of blood banking and transfusion is relevant to explore the impact of anemia on transfusion efficacy. These results extend an existing literature where mouse models have been used to explore the impact of refrigerated storage 23–30 and the role of the recipient's genetic background on the 24 h PTR 31 …”

Section: Discussionsupporting

confidence: 79%

Erythropoietin downregulates red blood cell clearance, increasing transfusion efficacy in severely anemic recipients

Casimir,

Colard,

Dussiot

et al. 2023

American J Hematol

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Red blood cells (RBC) transfusion is used to alleviate symptoms and prevent complications in anemic patients by restoring oxygen delivery to tissues. RBC transfusion efficacy, that can be measured by a rise in hemoglobin (Hb) concentration, is influenced by donor‐, product‐, and recipient‐related characteristics. In some studies, severe pre‐transfusion anemia is associated with a greater than expected Hb increment following transfusion but the biological mechanism underpinning this relationship remains poorly understood. We conducted a prospective study in critically ill patients and quantified Hb increment following one RBC transfusion. In a murine model, we investigated the possibility that, in conjunction with the host erythropoietic response, the persistence of transfused donor RBC is improved to maintain a highest RBC biomass. We confirmed a correlation between a greater Hb increment and a deeper pre‐transfusion anemia in a cohort of 17 patients. In the mouse model, Hb increment and post‐transfusion recovery were increased in anemic recipients. Post‐transfusion RBC recovery was improved in hypoxic mice or those receiving an erythropoiesis‐stimulating agent and decreased in those treated with erythropoietin (EPO)‐neutralizing antibodies, suggesting that EPO signaling is necessary to observe this effect. Irradiated recipients also showed decreased post‐transfusion RBC recovery. The EPO‐induced post‐transfusion RBC recovery improvement was abrogated in irradiated or in macrophage‐depleted recipients, but maintained in splenectomized recipients, suggesting a mechanism requiring erythroid progenitors and macrophages, but which is not spleen‐specific. Our study highlights a physiological role of EPO in downregulating post‐transfusion RBC clearance, contributing to maintain a vital RBC biomass to rapidly cope with hypoxemia.

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Section: Discussionsupporting

confidence: 79%

Erythropoietin downregulates red blood cell clearance, increasing transfusion efficacy in severely anemic recipients

Casimir,

Colard,

Dussiot

et al. 2023

American J Hematol

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“…On the morning of PTR experiments, a leukoreduced RBC unit (60% hematocrit) was prepared from mice whose RBCs were biotinylated in vivo (1mg/300μL in PBS injected into the retro-orbital sinus)(26). Stored RBC units were spiked 1:5 with fresh biotinylated RBC units as a loading control.…”

Section: Methodsmentioning

confidence: 99%

Reticulocytes in donor RBC units enhance RBC alloimmunization

Thomas

Qiu

Kim

et al. 2023

Preprint

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Although red blood cell (RBC) transfusions save lives, some patients develop clinically-significant alloantibodies against donor blood group antigens, which then have adverse effects in multiple clinical settings. Few effective measures exist to prevent RBC alloimmunization and/or eliminate alloantibodies in sensitized patients. Donor-related factors may influence alloimmunization; thus, there is an unmet clinical need to identify which RBC units are immunogenic. Repeat volunteer blood donors and donors on iron supplements have elevated reticulocyte counts compared to healthy non-donors. Early reticulocytes retain mitochondria and other components, which may act as danger signals in immune responses. Herein, we tested whether reticulocytes in donor RBC units could enhance RBC alloimmunization. Using a murine model, we demonstrate that transfusing donor RBC units with increased reticulocyte frequencies dose-dependently increase RBC alloimmunization rates and alloantibody levels. Transfusing reticulocyte-rich RBC units was associated with increased RBC clearance from the circulation and a robust proinflammatory cytokine response. As compared to previously reported post-transfusion RBC consumption patterns, erythrophagocytosis from reticulocyte-rich units was increasingly performed by splenic B cells. These data suggest that reticulocytes in a donated RBC unit impact the quality of blood transfused, are targeted to a distinct compartment, and may be an underappreciated risk factor for RBC alloimmunization.

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“…Of note, alterations of this pathway are critical for regulating abnormal hematopoiesis in aging mice and humans [ 105 ]. Dietary interventions that alter fatty acyl membrane composition predispose, or protect, lipids from peroxidation [ 106 ], a hallmark of ferroptosis that regulates RBC extravascular hemolysis; the latter is—at least in part modulated by the activity of the ferrireductase STEAP3 [ 107 ]. Pathways exist in mature RBCs to cope with lipid peroxidation; for example, via glutathionylation by GPX4 —which is present and active in mature erythrocytes [ 33 ].…”

Section: Rbc Metabolism Beyond Glycolysismentioning

confidence: 99%

Red Blood Cell Metabolism In Vivo and In Vitro

et al. 2023

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Red blood cells (RBC) are the most abundant cell in the human body, with a central role in oxygen transport and its delivery to tissues. However, omics technologies recently revealed the unanticipated complexity of the RBC proteome and metabolome, paving the way for a reinterpretation of the mechanisms by which RBC metabolism regulates systems biology beyond oxygen transport. The new data and analytical tools also informed the dissection of the changes that RBCs undergo during refrigerated storage under blood bank conditions, a logistic necessity that makes >100 million units available for life-saving transfusions every year worldwide. In this narrative review, we summarize the last decade of advances in the field of RBC metabolism in vivo and in the blood bank in vitro, a narrative largely influenced by the authors’ own journeys in this field. We hope that this review will stimulate further research in this interesting and medically important area or, at least, serve as a testament to our fascination with this simple, yet complex, cell.

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Deuterated Linoleic Acid Attenuates the RBC Storage Lesion in a Mouse Model of Poor RBC Storage

Cited by 14 publications

References 66 publications

Erythropoietin downregulates red blood cell clearance, increasing transfusion efficacy in severely anemic recipients

Erythropoietin downregulates red blood cell clearance, increasing transfusion efficacy in severely anemic recipients

Reticulocytes in donor RBC units enhance RBC alloimmunization

Red Blood Cell Metabolism In Vivo and In Vitro

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